1. Field of the Invention
The present invention relates generally to the fields of obstetrics and/or perinatal medicine. More particularly the invention relates to repair of pre-parturition rupture of the amniotic fluid sac.
2. Description of Related Art
Premature rupture of membranes (PROM) during the second and early third trimester of human pregnancy creates a management dilemma for obstetricians. There are currently many management protocols for PROM. Recent literature argues the risks and benefits of tocolytic agents, antibiotics, and corticosteroid injections primarily for delaying delivery, preventing intraamniotic infection, and enhancing fetal maturity, respectively, in the event of almost certain preterm delivery. However, to date, no true accepted treatment for PROM exists. Medline searches of this topic reveal only scant data in Italian studies on intracervical instillation of fibrin glue, and Japanese attempts at mechanical blockage of the cervix using double balloon-tipped catheters.
The ideal therapy for PROM in the absence of chorioamnionitis, and deciduitis (infections implicated in premature rupture and preterm labor) would seem to be to recreate an intact amniotic fluid sac using a benign sealant injected into the amniotic sac using needles no bigger than those now commonly used for amniocentesis. By recreating the integrity of the amnion, such a technique would provide a barrier to ascending infection from the normal bacterial flora of the cervix and vagina commonly isolated in most all obstetric and gynecologic infections. Such a technique would also allow reaccumulation of normal amniotic fluid volumes, thus protecting the fetus from compression of its own umbilical cord.
Chicken egg white is a cross species analog to amniotic fluid, providing protection, cushioning, and nutritive substances essential to the survival of the unborn chick. The cross linking of this colloid substance at the site of membrane rupture in the human gestation may provide an adequate sealant in the event of PROM. The inherent properties of egg white colloid include immiscibility with water (hydrophobic), thus creating a bolus effect when encountering the leakage site after injection into a water filled cavity. The most gelatinous portion of the thick egg white component is of substantially low enough viscosity to allow injection via a standard 18 to 20 gauge spinal needle commonly used for amniocentesis.
The present invention overcomes these and other drawbacks of the prior art by providing methods and compositions for treating premature rupture of membranes (PROM) during pregnancy. The methods and compositions provided result in prolonged gestation, decreased risk of infection and umbilical cord compression, and an increased likelihood of a mature fetus.
In one aspect, the invention provides a method of sealing a ruptured amniotic membrane by introducing an effective amount of an avian thick egg white composition into an amniotic fluid sac of a mammal. It is envisioned that the thick egg white from any type of avian egg will be effective in the present invention. The preferred composition will include chicken thick egg white. For administration of the into the amniotic fluid sac of a mammal, it is preferred that the composition additionally include any known pharmaceutically acceptable carrier. It is not believed that the pharmaceutically acceptable carrier is absolutely necessary in the method of the invention, however.
It is believed that the component of thick egg white that is most important in accomplishing the objectives of the invention is the protein known as ovomucin. Therefore, in preferred embodiments, the composition for use in the method of the invention includes isolated and purified ovomucin or an ovomucin composition. It is envisioned that the ovomucin in the composition of the invention may be present in concentrations of about 1 to 90 percent by weight. It will be understood that this range of concentrations includes all integers and fractions contained between the range of 1 to 90 percent. That is, the range is meant to include concentrations of 1, 2, 3, 4 . . . 10, 11, 12, 13, 14, . . . 20, 21, 22, 23, 24, . . . 30, 31, 32, 33, 34, . . . 50, 51, 52, 53, 54, . . . 80, 81, 82, 83, 84, . . . and so on, including fractions of a percentage, such as 1.1, 1.2, 1.3, . . . 2.1, 2.2, 2.3, . . . 5.1, 5.2, 5.3, . . . 10.1, 10.2, 10.3. . . and so on up to about 90 percent by weight.
In certain preferred embodiments, the thick egg white composition further comprises one or more antibiotics.
The thick egg white composition for use in the method of the invention will typically be introduced into the amniotic sac by an injection procedure, such as an amnioinfusion procedure.
Another aspect of the invention provides a method of enhancing the integrity of a ruptured amniotic membrane by contacting the ruptured amniotic membrane with an effective amount of an avian egg white glycoprotein composition. Preferably, the avian egg white composition will be a chicken thick egg white composition. Most preferably, the thick egg white composition will include a pharmaceutically acceptable carrier. The thick egg white composition will generally comprise an ovomucin composition where the ovomucin will be isolated substantially away from other thick egg white components and purified. The ovomucin may be present in concentrations of 1 to about 90 percent by weight. In certain preferred embodiments, the thick egg white composition will further include one or more antibiotics.
It is envisioned that the thick egg white composition will typically be introduced into the amniotic sac of a patient using an injection procedure. Preferably, the injection procedure will be an amnioinfusion procedure, such as amniocentesis.
Another embodiment of the present invention provides a pharmaceutical amniotic membrane sealant composition comprising an effective amount of a sterile avian egg white glycoprotein composition and one or more pharmaceutically acceptable preservatives. The composition of the invention may further include a pharmaceutically acceptable carrier and/or at least one antimicrobial agent in a therapeutically effective amount.
The present invention further provides a kit for use in a method of sealing a ruptured amniotic membrane including a thick egg white glycoprotein composition in a suitable vial or container. Preferably, the thick egg white composition will include isolated and purified ovomucin with a purity of about 80% to about 95%. The egg white composition may be present in the vial in powder form or gel form or in a solution including a pharmaceutically acceptable preservative and/or a pharmaceutically acceptable carrier. In certain aspects, such as when the composition is in powder or gel form, a pharmaceutically acceptable carrier may be added directly to the vial, mixed gently, drawn into an appropriate needle for injection, and injected into a patient having a ruptured amniotic membrane.